NO has been the most intensely studied signalling molecule for more than a decade. Produced by NO synthases (NOS), it regulates blood pressure, contributes to the immune response, controls neurotransmission, and participates in cell differentiation; in fact, the list of the physiological functions for which NO action is important continues to grow. Nonetheless, it has long remained an open question whether NO is also actually necessary for animal development. This uncertainty was mainly due to the fact that the mammalian genome encodes three NOS genes with partially overlapping function; because these genes may compensate for each other if one of them is mutated, an essential function for NO would be masked.

In the new work, researchers Grigori Enikolopov, Michael Regulski, and their colleagues from the Cold Spring Harbor Laboratory show that, indeed, NOS is crucial for development in the fruit fly, Drosophila, and that flies lacking the gene die as embryos. The work takes advantage of the fact that, unlike those of mammals, the genome of the fruit fly has only one NOS gene and is thus more amenable to mutagenesis and genetic analysis. After a large genetic screen, the researchers found several mutations that inactivate the Drosophila NOS gene. Their work provides the first conclusive evidence that NOS function is essential for the development of an organism.

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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
25-Oct-2004